Model systems for studying carcinogenesis directly in human target tissues (bronchus, colon, breast, esophagus and pancreatic duct) have been developed to assess the following: a) mechanisms of carcinogenesis in human cells; b) variation in carcinogenic susceptibility among individuals; and c) validity of the extrapolation of carcinogenesis data from experimental animals to the human situation. Metabolism of several classes of chemical procarcinogens is being studied in human tissues maintained under controlled experimental conditions. Investigations to date indicate that metabolic pathways and carcinogen-DNA adducts are qualitatively similar in human tissues and in tissues of experimental animals in which these chemicals are carcinogenic. A marked inter-individual variation in metabolism of benzo(a)pyrene has been found. A possible interaction between pulmonary macrophages and bronchial epithelium in the activation of benzo(a)pyrene during bronchogenic carcinogenesis has been identified. A human tissue- and cell-mediated mammalian mutagenesis assay has been developed. Chemical and physical carcinogens caused preneoplastic lesions in cultured and xenotransplanted human tissues.